Sphingosine-1 phosphate receptors (S1P) are found on the surface of many cell types. S1P receptors are activated by binding sphingosine-1 phosphate. There are five types of S1P receptors, each of which triggers distinct signal transduction pathways. S1P binding to S1P receptors may activate different cellular functions, including cell proliferation and differentiation, cell survival, cell invasion, lymphocyte trafficking, and cell migration.
FTY720 is an immunosuppressant prodrug that functions by antagonizing S1P receptors. In its active, phosphorylated state, FTY720 binds four of the five S1P receptors. FTY720 binding to S1P1 causes receptor activation and subsequent down-regulation trapping lymphocytes in secondary lymphoid organs. Currently, FTY720 is marketed to treat relapsing-remitting multiple sclerosis (MS). Previous publications describe broad classes of FTY720 analogs for use in selectively binding S1P receptors.